Serotonin regulation of T-cell subpopulations and of macrophage accessory function.
Young MR, Matthews JP.
Research Service, Hines VA Hospital, Hines, Illinois.
The role of serotonin as an immune modulator was investigated by measuring the functional competence of T cells from control mice versus from mice whose intracellular stores of serotonin had been depleted by pretreatment with p-chlorophenylalanine (PCPA). While the proportions of splenic CD4+ and CD8+ T cells isolated from control and PCPA-treated mice were similar, the level of expression of the alpha-chain interleukin-2 receptor (IL-2R) was reduced on splenic CD4+ cells but not on CD8+ cells. Culture with the T-cell mitogen concanavalin A (Con A) failed to induce expression of the IL-2R on either CD4+ or CD8+ cells of PCPA-treated mice, although IL-2R was induced on control cells. The proliferative response to Con A by these spleen cells from PCPA-treated mice was also reduced compared to that by control spleen cells. Both expression of IL-2R and proliferation in response to Con A by spleen cells from serotonin-depleted mice were increased or completely restored by supplementation of the cultures with serotonin. Studies to identify the mechanisms for the reduction in T-cell activation when serotonin levels were reduced implicated a defect in the capacity of macrophages from PCPA-treated mice to provide accessory help for T-cell activation. Splenic macrophages from control mice were able to restore the blastogenic capability of lymphocytes from PCPA-treated mice, although macrophages from PCPA-treated mice were unable to support normal lymphocyte blastogenesis unless the cultures were supplemented with serotonin. These results show the requirement of autologous serotonin for optimal T-cell activation and suggest the importance of serotonin in macrophage accessory function for T-cell activation.
Publication Types:
PMID: 7890297 [PubMed - indexed for MEDLINE]
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